Wednesday, March 02, 2016

When philosophers talk about genomes

Postgenomics is a compendium of twelve scholarly articles by philosophers and sociologists who write about the implication of the human genome sequence and subsequent work on interpreting the results. The volume is edited by Sarah Richardson, a professor in Social Sciences (History of Science) at Harvard University (Boston, Massachusetts, USA), and by Hallam Stevens, a professor of History at Nanyang Technology University in Singapore (Singapore).

The first essay is by Stevens and Richardson and it outlines the goal of the book.

In the wake of the completion of the major genome sequencing project, a more quiescent decade followed, as scientists, science studies scholars, and activists waited to see what the next big breakthroughs would be. The essays in this book step into this open space to put the myriad changes instantiated within the life sciences in the post-HGP period in historical, social, and political context and thereby begin to make sense of them. Exploring the uncertain, transitional, and contested terrain of postgenomics, the contributors adopt a posture of critical reflection mixed with surprise and appreciation for the insights brought by the postgenomic era. They examine the continuities and ruptures, as well as the micro and macro transformations, instituted by the spread of genomic data and technologies throughout the life sciences over the past decade. They balance critiques of the practices and prospects of genome science with grounded analysis of the conceptual shifts and changes in everyday practices initiated by genomic data and technologies in knowledge production. Collectively, these essays document how postgenomics is reshaping debates over genetic determinism, reductionism, the role of the social and the environmental in human health and disease, and even the notion of the genome itself.

Most of the essays are boring. I'll not bother to summarize them. The main theme of all of the essays is that wonderful things have come out of the human genome project and our view of genes and genomics has been transformed.

You can get a good idea of the tone from a paragraph in the introductory essay. Stevens and Richardson acknowledge that the ENCODE results were controversial and that many scientists disputed the ENCODE definition of "function." They go on to say,

But the ENCODE controversy is not just about hype, methodology, and organization—it also shows how far biologists are from agreement on an account of genomic action. It is not merely that the definitions of fundamental terms—such as "functionality"—are still open to contestation. The debate points to significant uncertainty about the overlapping roles (and relative importance) of evolution, DNA structure, transcription, and regulation in the human genome. Genes, the New York Times reported in 2008, are having an "identity crisis": acknowledgement of the importance of epigenetic marks, alternative splicing, post-transcriptional modification, and noncoding RNA have rendered the concept almost meaningless.

This idea, that scientists are confused and bewildered by the human genome, occurs in many of the essays. It reflects the view from the outside, where even historians and philosophers are having trouble sorting out truth and fact from myth and hyperbole. Frankly, my concept of what a "gene" is hasn't changed from what it was in the 1970s [What Is a Gene?]. I don't know what they're talking about. Maybe they're talking about some people who had some bizarre, nonscientific, definition of a gene? Maybe they're talking about philosophers?

But sorting out the truth is their job, isn't it?

Let's look at the second essay in the book. The author is Evelyn Fox Keller an emeritus professor of the History and Philosphy of Science at MIT (Boston, Massachusetts, USA). She has a P.D. in physics and her thesis topic was on gene expression in bacteriophage lambda. She has won a MacArthur Fellowship and a Guggenheim Fellowship. Those are good credentials. She should know what she is talking about.

The title of her essay is "The Postgenomic Genome." The gist of her claim is that the study of the human genome has "turned our understanding of the basic role of the genome on its head." She claims that instead of being a sloppy bunch of chromosomes full of junk, the genome is actually "an exquisitely sensitive and reactive system."

Throughout the history of classical genetics and early molecular biology, the science of genetics focused on genes, widely assumed to be the active agents that lead to the production of phenotypic traits. Similarly, the genome (a term originally introduced in 1920) was regarded as the full complement of an organism's genes. Indeed, I claim that this assumption is largely responsible for the widespread interpretation of the large amounts of noncoding DNA identified in the 1970s and 1980s as "junk DNA." Genomic research has not only made this interpretation untenable but also, I argue, supports a major transformation in our understanding of the genome—a shift from an earlier conception of the genome (the pregenomic genome) as an effectively static collection of active genes (separated by "junk DNA") to that of a dynamic and reactive system (the postgenomic genome) dedicated to the regulation of protein-coding sequences of DNA. In short, it supports a new framework of genetic causality.

Of particular importance to this new perception of the genome were the early results of ENCODE, a project aimed at an exhaustive examination of the functional properties of genomic sequences. These results definitely put to rest the assumption that non-protein-coding DNA is nonfunctional. By the latest count, only 1.2 percent of the DNA appears to be devoted to protein coding, while the rest of the genome is nonetheless pervasively transcribed, generating transcripts employed in complex levels of regulation heretofore unsuspected.

This is not a view of history that I support and it is not a view of the truth, either. As I have said repeatedly, there was never a time when knowledgeable scientists thought that all noncoding DNA was useless junk. I can sympathize, barely, with scientists who don't understand the history of their field but here we are dealing with a supposed expert in the history and philosophy of science. I hold her to a higher standard.

She has not met that standard. Her explanation of the meaning of "junk DNA" is misleading.

She has also failed to meet the standard in her interpretation of published experimental results. Scientists can disagree over how much of the genome specifies functional RNAs and Evelyn Fox Keller is perfectly entitled to side with those who support the idea that much of our genome is devoted to producing regulatory RNAs. She is not entitled to lie by implication as she does here. This book is intended for sociologists and philosophers and any of those people who read this paragraph would conclude that the science is settled—ENCODE was right about function. That's disingenuous. The best she could say in support of her claim is that there is a controversy and she sides with ENCODE. If she wanted to be even more correct in 2015, she could have said that hers is the minority view among experts. She could have mentioned that the ENCODE Consortium has partially retracted their claim. That's what an expert historian and philosopher of science should do.

You won't be surprised to learn that Evelyn Fox Keller perpetuates the myth that experts were surprised at the "low" number of genes when the draft sequence of the human genome was published in 2001. She seems to get much of her information from press releases and the popular press. She points out, correctly, that at the beginning of the Human Genome Project (HGP) the experts though that much of our genome was junk. But she errs in claiming that in the postgenomic era that idea gave way to a new metaphor: "dark matter of the genome."

It's not that some people didn't start writing about "dark matter" ... of course they did. That was the group suffering from the Deflated Ego Problem. They never liked the idea of junk DNA so they focused on the idea that most of the genome was a mystery. According to them, we don't know what's in our genome. It could be full of functional stuff.

That idea became popular with science writers who always like a mystery but an academic historian of science should know better. She doesn't ...

This shift in metaphor—from junk DNA to dark matter—well captures the transformation in conceptual framework that is at the heart of my subject. It was neatly described in a 2003 article on "The Unseen Genome" in Scientific American, where the author, W. Wayt Gibbs, wrote, "Journals and conferences have been buzzing with the new evidence that contradicts conventional notions that genes, those sections of DNA that encode proteins, are the sole mainstay of heredity and the complete blueprint for all life. Much as dark matter influences the fate of galaxies, dark parts of the genome exert control over the development and the distinctive traits of all organisms, from bacteria to humans. The genome is home to many more actors than just the protein-coding genes." Of course, changes in conceptual framework do not occur overnight, nor do they proceed without controversy, and this case is no exception. The question of just how important non-protein-coding DNA is to development, evolution, or medical genetics remains under dispute. For biologists as for physicists, the term "dark matter" remains a placeholder for ignorance. Yet reports echoing, updating, and augmenting Gobbs's brief summary seem to be appearing in the literature with ever-increasing frequency.

The truth is quite different. No knowledgeable scientists ever thought that protein-coding genes were the only functional thing in our genome. For one thing, no knowledgeable scientist ever thought that all genes were protein-coding. For another, they were all aware of the importance of regulatory sequences based on solid evidence spanning fifty years of work. Knowledgeable scientists do not think that junk DNA is a reflection of our ignorance as the term "dark matter" implies. Instead, they are well aware of the Five Things You Should Know if You Want to Participate in the Junk DNA Debate.

I don't think Evelyn Fox Keller knows any of the positive evidence for junk DNA. She could not write such rubbish about a transformation in conceptual framework if she did. Does this matter? Yes it does. She is writing the history of a field as a professor of the history and philosophy of science. I expect better.

Can it get any worse? You bet.

Evelyn Fox Keller is a big fan of .... wait for it ... John Mattick!!

She even includes a figure from one of his 2011 papers (Mattick, 2011). I've scanned the figure from her essay (left) but I've also included the actual figure from Mattick's paper (below) (Mattick, 2011). I hope most of you remember the Dog's Ass Plot so I don't have to explain what's wrong with these figures. (It's interesting that all you have to do is Goggle "John Mattick" to find out why these kind of plots are so stupid. Critical posts are on the second page of the google search.)

Here's what Keller thinks of Mattick.

Of particular shock value were the dicoveries, first, of how few genes the human genome contained (discussed above) and, second, of how small a portion of the genome's structure is devoted to protein-coding sequences. In a review article published in 2004, [Mattick, 2004] John Mattick published a graph displaying the ratio of noncoding DNA to total genomic DNA as a function of developmental complexity. Prokaryotes have less than 25 percent noncoding DNA; simple eukaryotes have between 25 and 50 percent noncoding DNA; and more complex fungi, plants, and animals have more than 50 percent, rising to approximately 98.5 percent in humans ...

Mattick estimated the proportion of human DNA coding for proteins at 1.5 percent; since then, estimates have decreased to 1 percent. The obvious question is, what is the remaining 98.5-99 percent for?

In 2003, the research consortium ENCODE (Encyclopedia of DNA Elements) was formed with the explicit mandate of addressing this question. More specifically, ENCODE was charged with the task of identifying all the functional elements in the human genome. Early results of that effort (based on analysis of 1% of the genome) were reported in Nature in 2007, and they effectively put the kibosh on the hypothesis that noncoding DNA lacked function (i.e., that it was junk, "for" nothing but its own survival. They confirmed that the human genome was "pervasively transcribed" even where noncoding; and, finally, that noncoding sequences are often strongly conserved under evolution. Furthermore, they showed not only that noncoding DNA is extensively transcribed but also that the transcripts (now referred to as "noncoding RNA" or "ncRNA") are involved in many forms and levels of genetic reglation that had heretofore been unsuspected.

I suppose it's true that ENCODE "put the kibosh on the hypothesis that noncoding DNA lacked function" but who in the world advocated such a hypothesis? No knowledgeable scientist, especially in 2007, ever claimed that all noncoding DNA was junk. That's a myth, verging on a lie.

What's implied in her essay is the idea that a significant proportion of our genome is transcribed to produce functional regulatory RNAs. The facts are quite different. It's unlikely that such genes represent more than one percent of our genome even if there are 20,000 of them. That still leaves 98% unaccounted for by her criteria but Evelyn Fox Keller doesn't mention that.

Instead, she says,

Genetics is not just about genes and what they code for. It is also about how the DNA sequences that give rise to proteins are transcribed, spliced, and translated into amino acid sequences, in the appropriate amounts at the appropriate time and place; about how these, once assembled into proteins navigate or are transported to the sites where and when they are needed and so on. All of this requires coordination of an order of complexity only now beginning to be appreciated. And it is now believed that the ncRNA transcripts of the remaining 98-99 percent of the genome are central to this process.

Back in the late 1980s—before the human genome project began—I taught a course on how genes—both protein-coding and those that specify functional RNAs—are expressed and regulated. We also covered RNA processing and translational control. We discussed protein sorting and secretion. None of the basics have changed following the sequencing of the human genome and the several hundred million dollars spent on ENCODE. The only thing I can say is that papers published in the 1990s led to the understanding that regulatory RNAs played a more significant role that we may have thought earlier. That was a quantitative change in our under standing, not a revolution.

We did not then, nor do we now, think that there are more genes for regulatory RNAs that there are for protein-coding genes of genes for known funcational RNAs (e.g., tRNA ribosomal RNA, snRna etc.). If you believe the hype promoted by John Mattick and echoed by Evelyn Fox Keller, then there must be almost 100 different regulatory RNA genes for every protein-coding gene! Does that make any sense at all?

If Evelyn Fox Keller is wrong (she is) how does this happen? How can a distinguished professor of the history and philosophy of science at a leading university (MIT) make such a mess of it?

There must be something seriously wrong with the discipline (History and Philosophy of Science) if such shoddy work can be published in 2015.

I suppose it's inevitable, since the science itself—biochemistry, molecular biology, genomics—is in even worse shape. For example, Evelyn Fox Keller tells us at the end of her essay that she has published the same argument elsewhere. The reference is Keller (2014) and the journal is the Journal of Physiology. Keller's affiliation is: MIT, Program in Science, Technology, and Society. Even scientific reviewers can be fooled.

Just can't bear the thought that the discussion might be about biology rather than you, could you? Your calling Professor Moran "ignorant" and "lazy ass" implies that there is important info about the function of "Junk DNA" that he should know but doesn't. Put up or shut up Steve, tell us what this info is and how you learned about it. References please. Enquiring minds want to know!

Here are the 6 arguments.1. Cast doubt on the science.2. Question the scientists’ motives and integrity.3. Magnify any disagreements among the scientists; cite gadflies as authorities.4. Exaggerate the potential for harm from the science.5. Appeal to the importance of personal freedom.6. Object that acceptance of the science would repudiate some key philosophy.

Steve is going nuts with #2 here, with a bit of #4 thrown in for good measure.

With regard to serious questions, scientists are far from dismissive - they're usually the ones asking them.

It's just that "Why haven't you accounted for the obvious fact that bacteria have opinions and there are intelligent agents at work in the genome?" doesn't count as a serious question, so dismissiveness is actually rather charitable.

Steve, I notice you have had a blog of your own for 8 years with not one post. Go post your wisdom there, explain how science and biochemistry actually work, revolutionize our understanding. No doubt then Sandwalk's readers will leave to view your pearls and you will have won the day for truth.

Well, at least we can see Larry Moran has a dedicated block of defenders hard at work hounding his detractors.

We even have DGA googling me to scrounge for some rhetorical points.

and judmarc once again wants to deny the intelligent activity of bacteria ...well just because he doesnt see a brain stem there.

and Mikkel decides to copy and paste from a higher power as his attempt at a slam dunk.

you all still haven't learned the lesson that denying intelligence is a self-deteating strategy.

Science will accelerate discovery only when it concedes the apparent intelligence activity embedded in life and starts asking the how and what questions:

a)how is intelligence capability built into the genome?b)what methods are used to embedd information?c)Is the quantum world responsible for this embedding?d)how could we research it?e)what kind of equipment would we have to build to start a research program on the question of quantum effects integrating with DNA and RNA to create command and control mechanisms?

There are tons of questions we can ask and explore from an intelligent design standpoint.

I think the reason these questions aren't being asked is that ID is the harder nut to crack. non-teleolgoical step-wise change is the path of least resistance.

@Steve"and Mikkel decides to copy and paste from a higher power as his attempt at a slam dunk."

I take it with this comment that you agree that mindlessly referencing higher powers is old superstitious stupidity, right?

Because, I'm merely citing a human being that I agree with, I don't consider him a higher power. Because I agree that mindlessly citing "higher powers" is fallacious and without rational justification.

Oh, that's NOT why you wrote that? You actually DO believe in citing a "higher power" as an authority! You just don't believe Sean Carroll is a "higher power", but neither do I. So now you have to actually deal with the arguments instead of being mindlessly, self-refutingly dismissive.

You see, you are being a mindless science-denier, you are trying to dismiss the science by trying to impugn the integrity and personal motivations of the scientists here (including Larry Moran), and you are trying to score cheap points by claiming Larry and others will have a detrimental effect on science. You are in other words a textbook example of a mindless science-denialist. Rather than giving valid scientific arguments that deal with the subject matter (genetics, junk-DNA), you are trying to circumvent the process of debate and experimentation by just being a dismissive religious retard. Well, you have certainly succeeded at the latter part. Congratulations!

and judmarc once again wants to deny the intelligent activity of bacteria ...well just because he doesnt see a brain stem there.

Not even a single neuron, actually, much less an entire segment of a brain.

And since you don't see it either, you go with the first refuge of the ignorant, "quantum" nonsense. Quantum physics isn't a magic box you can shoehorn God or Designer nonsense into, it's full-fledged well studied science, and none of it turns bacteria into Nobel prizewinning geneticists, sorry. I've read many of the academic papers on bacterial mutation in response to environmental stressors; I know you haven't. None of it's about magic.

Steve, I didn't Google you; I just clicked your name on your comment, which leads to your Blogger profile.

For a biochemist or geneticist to search the intelligence capability built into the genome, would be redundant, since we already know about the genetic code and information stored in the genome and about epigenetics, although much detail remains. There is no evidence now of anything more than what has been seen, although much detail will be yet discovered. The methods used to embed information in the genome are known, the genetic code and epigenetics. There are no doubt quantum effects in DNA since all chemical bonding is described by quantum mechanics, as Linus Pauling showed about 90 years ago. This is researched by well educated biochemists throughout the world, using state of the art equipment, no doubt, while trying to preclude ideological biases from their studies. Your program of trying to find the underlying intelligence would indeed be a tough nut to crack, a non-existent nut to be cracked by an imaginary nutcracker; rather like NASA planning a mission to explore Narnia - there being no evident there, there, there would be no direction to pursue, no path to follow, no point. If some new phenomena concerning DNA or RNA are waiting to be discovered, and there probably are, they no doubt will be discovered in the course of more and more detailed work by professionals in the field, but not by ideologically driven programs

Hey, I'd really like to see a figure like Fig. 1 above done with real data. You can get the genome sizes from the Genome Size Database; the main problem would be finding data on the size of the protein-coding portion of the genome for most of those species. But I bet you could approximate: assume, for example, that most animals have approximately the same amount of protein-coding DNA. I'm guessing that you could do the same for single-celled eukaryotes and some other "groups".

I have fasta and GTF files for a huge number of species, and the scripts to do it and I could put together a more comprehensive version, but is it really needed? Also, it will be somewhat biased because the poor-quality draft genomes.

It's based on cherry-picking those portions of the real data that fit the preconception of the author. I mean an unbiased sample. Now of course the existing sample of whole genomes is highly biased toward small genomes. But you shouldn't need the whole-genome data to do this, and the genome-size data are much less biased.

Let me amplify a bit. Note that the species with the largest genome here is H. sapiens. This is not true even if you restrict yourself to mammals; no need to even mention salamanders. One of the plants is Arabidopsis, and the other two are illegible but are plants with similarly small genomes, even if you restrict yourself to angiosperms; no need to even mention ferns. Fugu clearly is not present, as that would upset the scenario. Etc.

Whoops, they did include Fugu. They give it around 85% non-protein-coding DNA, which actually seems about right. But is it really that much lower (if at all) in developmental complexity than Man, Pinnacle of Creation?

Steve, he gave you a direct, real-world reference that evolution is being used to solve problems that human designers can't. You have not responded, you're merely being in denial of the obvious fact that evolution can and does produce extremely complicated *designs*.

Steve, "You claim algorithms solve problems where intelligence can't. But what was responsible for making the choice to use the algorithm?"

A software designer made the decision to use evolutionary algorithms which are based on knowledge of biological evolution. In the case of the former, there's evidence yeah intelligence. In the case of the latter, not one single shred of evidence for intelligence has ever been shown by you, El or Tx. Zero, zilch, nothing, nada. The only thing you lot can come up with is 'evolution can't do this, evolution can't do that, blah blah blah'.When are you Steve going to cough up the evidence in favor of this intelligence?? Will you be the first creationist to deliver the proof for intelligence? Tx and El have failed so far, nothing beyond the standard 'evolution can't blah blah'.

But, hey, this (evolutionary algorithms) has been explained to you many, many times already.

but if you warm to the idea that genomes are intelligently programmed, then is does make perfect sense

Or in other words, "If you first believe this nonsense, then that other nonsense begins making sense."

Say Steve, does understanding intelligently programmed genomes (that are so "intelligent" they behave exactly as ordinary chemistry says they should - may as well say it takes intelligence for a rock to know it has to fall off a mountainside) also bring the understanding that bacteria have opinions, or is that something separate and discreet we have to learn about from you?

Taken each in isolation, any process in bacteria behave (as you put it) 'as ordinary chemistry says they should'. Yet, the elephant in the room is the question HOW all these myriad processes are controlled, regulated, and organized.

Ordinary chemistry says jack shit about that. Nut evolutionary biology has bucketloads of storytelling explanations to sweep it all under the rug.

That is why evolutionary biology is useless. it has jack shit to say about 98% of the work that was done PRIOR to any of these processes doing more that twiddling their thumbs.

You want us to believe that nature is non intelligent but through emergence it can *somehow* can imitate intelligence.

What fu@king woo shLT is that??!!

Its as if you want to say that evolution is more intelligent than MAN, because MAN could not come up with that algorithm on his own.

You are living in la-la land Mikkel. The only reason evolution works is precisely because it was designed by an intelligence. Those algorithms were designed precisely as we design software, by thinking and planning.

this is the ONLY logical explanation that avoids the woo of emergence.

If anyone is guilty of just making shit up it would be folks on this blog pretenting evolution is not an intelligent process or a product of a mind.

Yet, the elephant in the room is the question HOW all these myriad processes are controlled, regulated, and organized.

Ordinary chemistry says jack shit about that.

In fact we know a great deal about the subset of ordinary chemistry, biochemistry, that describes how all this works. A fellow you may have heard of, Larry Moran, wrote a textbook about it.

But now that we're getting into real science you have no earthly idea what is going on and so you fall back to comforting fairy stories that fit your limited understanding.

You wouldn't have to do this (or desperately call people liars) if you were simply willing to do the work necessary to learn and understand the science. But it somehow threatens your world view to learn simple scientific facts and theories that were already old when you were young. This isn't nearly cutting edge stuff.

Don't know about you, but if my world view gave me issues with simple, well-established scientific facts to the point that I had to imagine bacteria have opinions in order to make it work, I'd find myself a world view that works better with reality.

some animal-wide system of genetic control functions to turn specific genes on and off as needed throughout the life of the organism—and that such a system functions during the development of an animal from egg to adult as different cell types are being constructed. the nonprotein-coding regions of DNA that regulate and control gene expression and the protein-coding regions of the genome together function as circuits. These circuits, which Davidson calls “developmental gene regulatory networks” (or dGRNs) control the embryological development of animals.once established, the complexity of the dGRNs as integrated circuits makes them stubbornly resistant to mutational change—a point he has stressed in nearly every publication on the topic over the past fifteen years.Developmental gene regulatory networks resist mutational change because they are organized hierarchically. As Davidson emphasizes, mutations affecting the dGRNs that regulate body-plan development lead to “catastrophic loss of the body part or loss of viability altogether.Davidson’s findings present a profound challenge to the adequacy of the neo-Darwinian mechanism. Engineers have long understood that the more functionally integrated a system is, the more difficult it is to change any part of it without damaging or destroying the system as a whole. Davidson’s work confirms that this principle applies to developing organisms in spades. The system of gene regulation that controls animal-body-plan development is exquisitely integrated, so that significant alterations in these gene regulatory networks inevitably damage or destroy the developing animal.

Say goodbye to mutations and NS as the mechanism for new body plans.....

A nonsensical quote from a nonsensical book. Small changes to transcription factor binding sites can alter their affinities for transcription factors by small degrees, thus allowing small changes in morphology. No macromutation necessary.

JohnDevelopmental gene regulatory networks resist mutational change because they are organized hierarchically. As Davidson emphasizes, mutations affecting the dGRNs that regulate body-plan development lead to “catastrophic loss of the body part or loss of viability altogether.Davidson’s findings present a profound challenge to the adequacy of the neo-Darwinian mechanism

It should be clear from John's comment that the creationist argument is a non-sequitur. There are known mechanisms by which small changes in morphology can occur. Stephen Meyer, as is his wont, is using his ignorance in place of an argument.

Developmental gene regulatory networks resist mutational change because they are organized hierarchically. As Davidson emphasizes, mutations affecting the dGRNs that regulate body-plan development lead to “catastrophic loss of the body part or loss of viability altogether.Davidson’s findings present a profound challenge to the adequacy of the neo-Darwinian mechanism

This is such complete horse manure. Many, many books and papers have been written about changes in developmental gene regulatory networks that trace particular changes in these networks to specific morphological changes in *viable* descendants.

so Davidson got it wrong then? Because Meyer just repeats Davidsons research. Mind to give a example of changes in developmental gene regulatory networks that trace particular changes in these networks to specific morphological changes in *viable* descendants.??

"This is such complete horse manure. Many, many books and papers have been written about changes in developmental gene regulatory networks that trace particular changes in these networks to specific morphological changes in *viable* descendants."

Meyer is specifically talking about mutations to dGRE's. Can you show evidence of beneficial mutations causing morphological changes?

No. That lying sack of shit, Stephen Meyer, got Davidson's writings wrong, probably deliberately. As Davidson said himself in response to this same claim when it was made by Meyer's partner in crime Paul Nelson:

Of course I would not disagree for one second about the importance of adaptive selection for species specific characters of all kinds, whether on protein or regulatory sequences.

Adding (to Jerry Coyne):

I admire your willingness to take on creationists in public; I find their views so antediluvian that I can only ignore them.

I would advise you to do the same, Bill Cole. I don't know how many more examples you need to convince you that, when evolutionists and creationists disagree, the creationists are always wrong. Always.

It should also be added that, if it is true that body plans are now very sensitive to mutations in DGRN's such that mutations are highly likely to have deleterious effects (which I don't doubt), that does not in anyway demonstrate that such networks could not have arisen thru evolution. In their early evolutionary stages they would not have been so sensitive.

It's like playing a game of Jenga: The more complex the tower, the more difficult it is to pull out a block without the whole thing coming crashing down.

Mind to give a example of changes in developmental gene regulatory networks that trace particular changes in these networks to specific morphological changes in *viable* descendants.??

Just one example? Heck, there's an entire *branch* of evolutionary biology, called "evolutionary developmental biology," or "evo-devo" for short, devoted to just these sorts of evolutionary morphological changes and the mutations in developmental regulatory genes that cause them. For numerous academic papers and several books on this, Google Sean B. Carroll (an evolutionary biologist, not Sean Carroll the physicist).

Long before the Human Genome Project was even a tinkle in James Watson's eye, I entered a very fine university with the intention of getting a PhD in the sociology of science. I did get the degree, but in another specialty, because of exactly this kind of nonsense. Among other things, I discovered that sociologists and, particularly, philosophers of science were all talking to each other-- and not to real working scientists. One philosopher of science had done ALL of his research in the library reading publication records. He had no idea how university chemistry labs (which I as studying at the time) function. He was completely unaware, for instance, that grad students and post-docs work on serious research projects, often published in top journals. He explained to me with a sneer that they were just "practicing." And that was a well-respected philosopher of science at that very fine university!

Larry Moran is absolutely spot on in this post. The fields of the sociology and philosophy of science were scandalously off base back when I knew them very well. Unfortunately, it sounds like nothing has changed.

You condemn E.F.Keller twice:1) first for claiming that any serious scientist ever thought that noncoding DNA lacked function, which you deny2) second for suggesting that noncoding DNA has a function, which you deny.You can't have both.If you put some proportions in there, you should at least agree with her that people have long thought (and many continue to do so) that "most" noncoding DNA doesn't have a function.Whether this belief is still held is another question, and it will obviously depend on what we mean by function. But you seem to assume that because you haven't changed, nothing did. You sure do hold that belief, and many of your colleagues do too. But (and I'd love to see empirical data on that) if a considerable proportion of a scientific community starts saying otherwise, are we not warranted in speaking of a transformation? Whether you (or I) think they're right or wrong doesn't make a difference to whether there was such a change (and I'd guess there was, otherwise we wouldn't be rambling about that all the time).If there was a change, good or bad, it's worth trying to understand why. You think it's because people are stupid and ENCODE's had good PR, but I don't think I'm alone finding this explanation somewhat unsatisfying.

PUH-LEEZE Pierr-Luc, read a little bit about the issue before you try this 'canned response' we have seen many times!

You condemn E.F.Keller twice:1) first for claiming that any serious scientist ever thought that noncoding DNA lacked function, which you deny2) second for suggesting that noncoding DNA has a function, which you deny.You can't have both.

THERE IS NO CONTRADICTION. What you leave out of your stupid statements is quantity-- percentage-- what FRACTION of non-coding DNA is functional? What *fraction* was believed to be functional, long before, decades before, ENCODE?

Your next phrase "noncoding DNA has a function, which you deny" is likewise misleading because here you say Larry said *no* non-coding DNA has a function. This is a lie.

Larry and many, many other critics have accurately pointed out, many times, that:

1. No knowledgeable scientist in genetics or molecular biology ever said *all* non-coding DNA was non-functional junk, nor that *no* non-coding DNA had function, nor that non-coding DNA was equal to any subset of junk.

2. *Some* non-coding DNA has a function-- a small fraction of the 3 billion basepairs in the genome. Scientists have known for decades about a long list of functions in non-coding DNA, such as, regulatory elements discovered in the 1950's, functional RNA genes, ribsomal RNA coding elements, etc. For DECADES we have known that some non-coding DNA was functional. The scientific argument was that, when you add all that functional stuff together, it's a small percentage of the genome. You have to divide it by the 3 billion base pairs in the genome. "Small percentage" is not "none", so you seriously misrepresented our position.

Like most no-junkists, you cannot understand the difference between junk is a subset of non-coding DNA and non-coding DNA is a subset of junk and you deliberately confuse them. Do you understand the difference between "some not all mammals are bats" and "some not all bats are mammals"? Do you understand that by substituting one for the other, you knock down a straw man of your construction?

What kind of rant is this?Have you even read the sentence starting with "If you put some proportions in there"? It's annoying to be accused of "deliberately confusing" something I just pointed out.Of course it's a matter or proportion, and that's why the post's treatment of Keller isn't fair. The question I was asking, and which we should ask, is whether there was a change in the way the scientific community (which is more than you or Moran) has perceived this proportion, and if so why. If you don't have anything constructive to say on that, please don't bother...

A basic problem with Keller's essay and with your comment is an apparent confusing of "non-coding DNA" with "non-functional DNA."

Coding DNA codes for proteins or for useful RNA's. Non-coding DNA includes promoters, other regulatory elements, centromere, telomeres, other structural elements, and other useful things. People who study DNA have known this for decades. Suggesting that this is news is inaccurate. People trying to write about the history of knowledge of DNA have an obligation to get this right, and Keller didn't.

Non-coding DNA also includes "junk" -- useless stuff. One can reasonably argue about how much of our DNA is junk, but one can't reasonably argue that regulatory elements, for example, are junk DNA -- or were ever thought to be junk DNA.

As someone who learned about promoters in the 1970's, I am in a position to say that the fact that some DNA that doesn't code for proteins is nonetheless useful is not a new idea.

I agree with bwilson, If the point of your comment is that perhaps the generally accepted view is that most non-coding DNA is functional, the first few paragraphs are so distracting that they should have been omitted.

The first two bits from Pierre-Luc are an accusation that Larry contradicted himself:

You condemn E.F.Keller twice:1) first for claiming that any serious scientist ever thought that noncoding DNA lacked function, which you deny2) second for suggesting that noncoding DNA has a function, which you deny.You can't have both.

This is a flat out accusation of contradiction, where none of us contradicted ourselves, and it cannot be saved by what follows.

Yes, I saw that Pierre-Luc followed this up with If you put some proportions in there, you should at least agree with her that people have long thought (and many continue to do so) that "most" noncoding DNA doesn't have a function.

First, Larry, and the proponents of the Junk DNA hypothesis did put proportions in there. It was the OPPONENTS of the Junk DNA hypothesis who took the proportions out.

But this statement is false too, for a different reason: you should at least agree with her [Keller] that people have long thought (and many continue to do so) that "most" noncoding DNA doesn't have a function.

It may be scientifically accurate, but it's not what Keller said! Keller didn't say "people have long thought (and many continue to do so) that "most" noncoding DNA doesn't have a function"!

Keller said that scientists believed ALL non-coding DNA was junk. You're rewriting what she wrote into something more reasonable, yes. More accurate, yes. So you're less wrong about the science, but only because you misrepresent her very wrong, deliberately intended, crystal clear lie, and you sew that pig's ear into a purse.

But (and I'd love to see empirical data on that) if a considerable proportion of a scientific community starts saying otherwise, are we not warranted in speaking of a transformation?

Sure there was a transformation. Prior to the 1960's, and well through for many, people tended towards the view that all of the genome did something. Then there was Ohno, various forms of 'selfish' DNA, the selective cost of additional bases, the bias for increase and against decrease ... so then, on the basis of empirical data and argument, the view transformed to only a proportion (of both coding and non-coding regions) having a function.

So you think people are transforming back? The period 1970-2010 was just a blip attributable to ignorance and prejudice?

You can't just parachute into history at one point and start your revision there.

To say that there was a transformation doesn't mean that it's justified, it would just mean that scientists talk differently today than they did 30y ago. I don't have enough information to say whether there is such a difference, but I'm saying that if we argue against Keller, that should be the object of the argument.

To say that there was a transformation doesn't mean that it's justified

To say ANYTHING doesn't mean it's justified! They were right, now they're wrong; one day they'll be right again ... ?

The justification came from the detail - from genetic load arguments, from biases, element types and cross-taxon analysis of sequence conservation. ie DATA. It was initially resisted, but the evidence won out. So at the moment, the ball is in the court of the 'perfectionists'.

Simply saying 'we don't know everything' can be a perennial justification for any position. We know enough, right now, to say with confidence that nonfunctional DNA is sufficient to account for the c value paradox. If there is some other way of accounting for it, it needs more than a 'maybe ... ', usually followed by a bad analogy.

@bwilson295:Since you seem to care, I wrote non-coding because 1) we all agree on what it means, contrarily to function.2) given that junk DNA is commonly defined as non-functional DNA, the very statement "junk DNA has a function" wouldn't even make sense.

We all know that functionality of some non-coding DNA isn't new -- the question is how much of it. Did that change or were people already fighting in the 70's between 'a lot' and 'very little'? If it changed, why?

When I learned about promoters in the early 1970's, I was a lowly undergrad with an interest in bird behavior. I didn't know if there was a controversy about how much of the genome was functional. All I knew was that the category non-coding DNA included functional elements.

Your use of "non-coding DNA" in this comment is inconsistent with your use of it in the previous comment.

Dr. Moran is parsing non-coding DNA into functional and non-functional components and insisting that the distinction is critical (only the latter being junk). I don't see that he contradicted himself. Keller used the terms carelessly, and apparently came to some poor conclusions about the history of knowledge of DNA function as a result.

I didn't mean to say he contradicted himself: the two mutually-exclusive statements were simply meant to show that his criticisms and lack of quantitative nuance are oversimplifying Keller's thesis. Sorry if this didn't get across.

I'll try to give a clear example. In the post above Moran quotes a passage where Keller writes:"The question of just how important non-protein-coding DNA is to development, evolution, or medical genetics remains under dispute."In answer to that, right below Moran writes:"The truth is quite different. No knowledgeable scientists ever thought that protein-coding genes were the only functional thing in our genome."Is that what she wrote?

I'm just disappointed to see people trying hard to misinterpret her words into mistakes, rather than making a genuine effort assessing what she's really trying to say. Put in very simple terms, that there was a slow transition from the vision of a genome as a repository of very few important bits that the cell would know when to pick up, to the genome as (to put it bluntly) a big, reactive mess.

There is in fact no dispute about how important non-protein-coding DNA is to development etc. Larry and everyone else knows it's crucial. The dispute is instead about how much of the non-coding DNA is functional. Keller's answer appears to be that most of it is. Larry's answer, which is the one the evidence supports, is around 10%.

Nobody here is misinterpreting Keller. Nor does your last sentence characterize anything I recognize in the history of science.

Of particular importance to this new perception of the genome were the early results of ENCODE, a project aimed at an exhaustive examination of the functional properties of genomic sequences. These results definitely put to rest the assumption that non-protein-coding DNA is nonfunctional.

Stop right there. WHO ASSUMED THAT? WE DIDN'T ASSUME THAT!

More specifically, ENCODE was charged with the task of identifying all the functional elements in the human genome. Early results of that effort (based on analysis of 1% of the genome) were reported in Nature in 2007, and they effectively put the kibosh on the hypothesis that noncoding DNA lacked function (i.e., that it was junk, "for" nothing but its own survival.)

WHOSE HYPOTHESIS!? NOT OUR HYPOTHESIS!

They [ENCODE] confirmed that the human genome was "pervasively transcribed" even where noncoding;

A fact already well-known to proponents of the Junk DNA hypothesis in the early 1970's, who pointed out that RNA transcripts aren't necessarily functional.

and, finally, [ENCODE confirmed] that noncoding sequences are often strongly conserved under evolution.

Totally deceptive and misleading. What does "often" mean? 7% of the genome? 8%? That's "often"? What the hell kind of deceptive language is this?

How much of the time do anti-junkists engage in outright lying? "Often".

Furthermore, they [ENCODE] showed not only that noncoding DNA is extensively transcribed but also that the transcripts (now referred to as "noncoding RNA" or "ncRNA") are involved in many forms and levels of genetic reglation that had heretofore been unsuspected.

Total lie. ENCODE never "showed" any such thing, they hypothesized it, and even the ENCODE authors themselves walked that back in their Kellis et al. 2014 paper.

And it is now believed that the ncRNA transcripts of the remaining 98-99 percent of the genome are central to this process.

Total lie. Not misleading, just a lie. Who believes that? Nobody! Even John Mattick and Stamatoyannopolis don't believe that! The latter put the functional part of the genome at 40%. Even Ewan Birney doesn't believe that! He walked back his fraction of the genome that's functional to 10% to 20%, optimistic. Nobody believes this!

What makes me think it's deliberately deceptive-- a lie-- is the way anti-junkists switch to passive voice "it is now believed" to hide the fact that they don't want to tell you who believes it! If you write an active voice sentence, you have to tell us who does the believing! But the sneaks deceptively switch to passive voice to conceal that they won't name who does the believing. Birney and Stamatoyannopolis don't believe it, who does? CITATION NEEDED.

The question of just how important non-protein-coding DNA is to development, evolution, or medical genetics remains under dispute.

There's one unobjectionable quote, out of many face-plants. That's one. Kudos to Pierre-Luc for citing the one sentence that Keller wrote that is not a total lie or otherwise complete bullshit.

Well, I might give a somewhat different flavor to Diogenes typically aggressive interpretation of Keller's statements, but I do agree she's importantly wrong, and that error taints her whole essay.

She writes, "These [ENCODE] results definitely put to rest the assumption that non-protein-coding DNA is nonfunctional." She is obviously confusing non-coding DNA with non-functional (junk) DNA, or she wouldn't write this.

At least since I was an undergraduate in the early 70's, nobody thought all non-coding DNA was non-functional. If she's this imprecise about basic definitions, can we trust her assessment of how ideas about DNA function have changed? (She might be right, of course, but would she know?)

Evelyn Fox Keller is a professor at MIT and her area of expertise is supposed to be the history of genetics and molecular biology.

She makes two fundamental mistakes in her book chapter and in the Journal of Physiology paper.

First, she misrepresents the history by propagating the the hoary myth that scientists once thought that all noncoding DNA was junk. This is demonstrably false if you take as your authority the scientists who were experts in the field. Every textbook since Watson's Molecular Biology of the Gene (1965) described examples of noncoding DNA with well-known functions.

Second, she errs in declaring that most of the human genome has a function. That is not the current consensus view among the experts in 2016. It's okay for her to give her personal opinion about which side of the controversy she favors but it is not okay for an expert on the history of science to ignore all the data that contradicts her personal opinion.

She has "conveniently" ignored all the evidence in favor of junk DNA and exaggerated all of the evidence against it. That's not how academic philosophers are supposed to behave.

The bottom line is this. Evelyn Fox Keller has misrepresented both the history and the science of genomics. That's a remarkable achievement for someone who's supposed to be an expert in the history of science.

I'm just disappointed to see people trying hard to misinterpret her words into mistakes, rather than making a genuine effort assessing what she's really trying to say. Put in very simple terms, that there was a slow transition from the vision of a genome as a repository of very few important bits that the cell would know when to pick up, to the genome as (to put it bluntly) a big, reactive mess.

I understand perfectly well what she's trying to say. She is trying to convince her readers that up until the publication of the human genome sequence most scientists though that the the only genes were protein-coding genes and that all noncoding DNA was junk.

She wants her readers to believe that there has been a revolution in the genomics era. She claims that the gene now has to be redefined and she claim that most of our genome has a function. That function is to regulate the expression of the 20,000 classic protein-coding genes.

"She claims that the gene now has to be redefined and she claim that most of our genome has a function. That function is to regulate the expression of the 20,000 classic protein-coding genes."

There are good reasons to think that protein-coding activities are just the tip of the genomic iceberg.

"UW scientists were stunned to discover that genomes use the genetic code to write two separate languages. One describes how proteins are made, and the other instructs the cell on how genes are controlled. One language is written on top of the other, which is why the second language remained hidden for so long."

Why? Because it is pretty apparent that trying to keep that horse down is about the unpleasant ideological implications that hyper-complexity invokes. The incompetent researchers behind the incompetent article are taxing the mutations/selection paradigm by suggesting a distinct regulatory language.

I find it rather curious that Wyatt Clark was more interested in coming up with what he apparently thought was a clever put-down than in defending Keller. If you have a cogent criticism, wouldn't you want to show the other side that you know the topic well and can see where they are wrong?Or do philosophers of science imagine science is just clever word games with no particular connection to reality?

Wyatt Clark: Cute. However, much of this thread has been biologists talking about about biology (that a philosopher has got wrong). Aren't philosophers supposed to care deeply about using words and phrases precisely?

"Or do philosophers of science imagine science is just clever word games with no particular connection to reality?"

I like this comment. It probably holds true for some philosophers of science, although they are probably in the minority. Some adhere to a strong form of scientific relativism, probably obtained from a poor reading of "The Structure of Scientific Revolutions," but even Kuhn himself disavows such views. I think if Thomas Kuhn had been more aware of the modern synthesis in evolutionary biology the concept of "incommensurability" would have been toned down a bit in "the Structure of Scientific Revolutions." He is a physicist though, and I think that influenced his perspective quite a bit.

Regarding hoary puccoon's comment: "I find it rather curious that Wyatt Clark was more interested in coming up with what he apparently thought was a clever put-down than in defending Keller."

Actually neither are true. My comment was not intended as a put down, nor do I wish to defend Keller. Good Sir, it seems your curiosity is misplaced.

Regarding Larry's comments: I think you do a fine job talking about "philosophy". In my opinion evolutionary biology is very philosophical. The discussions about function that have arisen due to [not well thought out] comments by individuals associated with ENCODE cut straight to the core of many problems and concepts central to philosophy; concepts that can be traced back to Aristotle and his discussions on "telos."

There are philosophers out there who likely disagree with Keller. I'm sure if you asked someone such as Daniel Dennett they would have a lot to say about Keller's statements, though I agree, it is unfortunate that the philosophy of science community has not chimed in more vocally on this particular discussion. It would be great to see more interaction between the two communities.

True, I am not male. Taking a pretty flower for a 'nym is much more typical of my gender, true?

I'm not sure anyone drew conclusions from one example about how philosophers of science as a group behave. Everyone but me generally confined themselves to Keller's mistakes and the fact that no other philosophers seem ready to correct her. And my dim view of philosophers of science comes from hard previous experience, not from this one incident.

I wasn't aware that philosophy could be discussed without pain. Philosophy seems to have developed a highly technical vocabulary without bothering to make the words refer to anything other than the writings of other philosophers.

My intent is not to trash philosophers. My intent is to trash egregious scientific falsehoods which Keller expressed in a tone of arrogant confidence.

However.

If philosophers of science don't correct this mountain of shit, the number of data points is not n=1. It reflects poorly on the whole field.

Likewise, when a genomicist or molecular biologist writes a mountain of shit about Junk DNA once believed to = noncoding DNA, if they go uncorrected, it reflects poorly on how we educate some scientists.

Now it's philosophy's turn.

Philosophers like to say that their discipline requires rigor. This is a powerful counterexample.

The discussions about function that have arisen due to [not well thought out] comments by individuals associated with ENCODE cut straight to the core of many problems and concepts central to philosophy; concepts that can be traced back to Aristotle and his discussions on "telos."

I've been following the function wars quite closely; in fact, I'm devoting an entire chapter to the discussion about function in the book I'm working on.

My conclusion hasn't changed. Neither philosophers, nor scientists posing as philosophers, have made a significant contribution to the issue by quibbling about the meaning of the word "function." It's like trying to define "gene" or "species." Biology is much too messy for those attempts to be universally successful.

Wyatt, can you give me an example that supports your implied claim? What have philosophers contributed to our understanding of which parts of the genome are functional and which parts are junk?

I am not big on the philosophy of science or biology. I much prefer symbolic logic and the likes of Hillary Putnam and Saul Kripke, but I'll give it a go...

How can you tell which parts of the genome are functional and which are junk if you believe biology is much to messy to define what one means by function? If your definition is messy, then so will be your distinctions between functional and junk parts of the genome. I will concede defining some parts can be messy, but not so much that the whole ordeal (defining, or at least discussing function) is futile.

There has been quite a bit written about the concept (I have a folder/.bib file with about 30 papers I can send you if you'd like). Maybe a good starting point would be Larry Wrights "Functions" (1973).

I believe Dan Graur cited Neander and her "Selected Effect" definition in his 2013 paper. Quoting Graur: "the “selected effect” function of a trait is the effect for which it was selected, or by which it is maintained." Under this definition, only parts of the genome under some form of selection have function. Is this the penultimate definition? I believe it is not without problems.

It would also be wise to familiarize yourself with the etiological and causal role definitions of function.

Have debates about the definition of function furthered our understanding of which parts of the genome are junk or functional? The question implies an alternative way to go about things: assigning the label functional or junk to parts of the genome, then working backwards to a definition. Perhaps there is no a-priori definition of function one can come to through mere philosophical argument. Perhaps the way we use the term in practice implies an a-posteriori/synthetic working definition masquerading as an analytic a-priori concept (again, I am still working with philosophical terms here).

Regarding your statement regarding the species concept, I'll leave you with a Dobzhansky quote lifted from "Speciation" (Coyne and Or) : "The manifest tendency of life toward formation of discrete arrays is not deducible from any a-priori considerations. It is simply a fact to be reckoned with."

How can you tell which parts of the genome are functional and which are junk if you believe biology is much to messy to define what one means by function? If your definition is messy, then so will be your distinctions between functional and junk parts of the genome. I will concede defining some parts can be messy, but not so much that the whole ordeal (defining, or at least discussing function) is futile.

Isn't it obvious that biologists use different definitions of function making it hard, in some cases, to decide whether a given bit of DNA is "functional" or junk?

If you think philosophers can help, then trying dealing with these examples. Do you have a definition that can determine whether the DNA is functional or not?

1. Active transposons in a genome.

2. The spacer DNA that's necessary to form the intron loop in splicing.

3. Bulk DNA if it has been selected for increasing genome size and therefore the size of the nucleus and the size of the cell.

4. The gene for surface antigens on red blood cells that determines whether you are type A or type B. That gene appears to be unnecessary because when it's broken (type O) there is no effect on survival.

5. The extra copies of the complement C4 gene that are common in many humans.

We have a good working definition of functional parts of the genome and that's whether they are playing a role in the survival of the individual and/or the species. Philosophers made no contribution to creating this definition. However, biologists know that it's often impossible to determine whether a given stretch of DNA is necessary or not. Furthermore, there are clear examples of bits that seem to be intuitively functional in some way but don't fit the working definition.

As far as I know, philosophers haven't been of any help resolving these ambiguities because they can't be resolved with an all-encompassing definition of "function." Not only that, philosophers usually don't have enough knowledge of evolution and the complexity of biology to make a contribution.

Unfortunately, that doesn't stop them from trying.

It's just like the attempt of philosophers to come up with a definition of "gene." All they've done is create lists of all the ambiguities and problems that biologists discovered for them. That's no help.

A grand, overarching definition of "function" is something that might be diverting to philosophers, but of minimal use to biologists or anyone else. It is probably more useful to focus on specific and clearly defined questions: Is this particular sequence transcribed? What happens to that transcript, or what does it do, thereafter? What effect would it have on the organism if this particular sequence was deleted? Etc. Such questions could be answered without ever having arrived at an agreed upon definition of "function."

I sense that philosophers have been planning to take control over how "science" and the "scientific method" is defined in science classrooms, by teaching that science is a branch of philosophy therefore only they are qualified to speak for its methods:

I read the thing, there is definitely no confusion about the authors' intent -- it is a clear example of "the whole genome is functional" type of hype, not a "the genome is one big mess and we did not quite realize that in the past" message.

Tell me something: Before regulatory elements in the genome were identified, how did people think the genome worked? That there was a single gene (or set of genes) coding for, say, each individual vertebra in the spinal column? I somehow doubt this.

Read Judson's "The Eighth Day of Creation" (a horrible title for an excellent history of science) if you're really interested in answering that. My take was that early on, the scientists were pretty much in a fog. They didn't even understand genes were made of DNA, not protein, until Oswald Avery's work in the early 1940's. And then, a lot of scientists didn't believe him.It was Monod, Jacob, and Lwoff at the Institute Pasteur who really started looking at how genes were turned on and off in the 1950's and early 60's.I don't think people had specific hypotheses about how genes worked before then.

I'm thinking the seventh day would be a metaphor for the transition from faith in supernatural mysticism to knowledge acquired through scientific investigation. Lots of people slept on that day however, and didn't notice.

Their data is consistent with the idea that most transcripts are just junk RNA produced by accidental transcription initiation. The most interesting result is that the parts of the genome that are accidentally transcribed at very low levels can change significantly over the course of 10,000 years or so.

Laurence A. Moran

Larry Moran is a Professor in the Department of Biochemistry at the University of Toronto. You can contact him by looking up his email address on the University of Toronto website.

Sandwalk

The Sandwalk is the path behind the home of Charles Darwin where he used to walk every day, thinking about science. You can see the path in the woods in the upper left-hand corner of this image.

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Quotations

The old argument of design in nature, as given by Paley, which formerly seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.Charles Darwin (c1880)Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Quotations

The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake.
Stephen Jay Gould (1982)
I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.
Stephen Jay Gould (2002) p.1339
The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change.
Stephen Jay Gould (1977)
Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance.
Stephen Jay Gould (1980)
Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change.
Stephen Jay Gould (1983) p.335
The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat.
Stephen Jay Gould (1999) p.84

Quotations

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is TrueI once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000
It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma
One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick
There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner
An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins
Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod
The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.